A Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD)

NCT04592341 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: WN297222020-001384-87
• Study Type: interventional
• Target: 192
• Locations: 8 countries
• Sites: 34

Brief Summary

This is a Phase II, multicenter, open-label, single arm, PD study in participants with early (prodromal to mild) AD to evaluate the effect of a once weekly (Q1W) dosing regimen of gantenerumab on deposited amyloid as measured by change from baseline to Week 104 (primary) and Week 208 in brain amyloid positron emission tomography (PET). The administration of gantenerumab as a single injection of Q1W will be investigated in this study, to simplify the dosing regimen for participants.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Brain Amyloid Load at Week 104 as Measured by [18F] Florbetaben Positron Emission Tomography (PET) Scan

  Screening amyloid PET scan was considered baseline evaluation.Brain amyloid load was quantified in terms of Standardized Uptake Value Ratio (SUVR),defined as ratio of tracer uptake in cortical composite target region of interest(ROI)to tracer uptake in reference ROI.Composite region: frontal,parietal,temporal,posterior cingulate cortex,anterior cingulate cortex. Reference ROI (whole cerebellum) was represented by weighted average of Cerebellum Ventral,Cerebellum Dorsal (left/right), Cerebellar White Matter.SUVR linearly transformed to standardized Centiloid Scale (CL) using formula CL=175.6xSUVR-174.2.CL ranges from \<0 to \>100, anchor points are 0=high-certainty amyloid negative scan and 100=amount of global amyloid deposition found in typical AD scan.

  Baseline, Week 104

Secondary Outcomes (9)

• Number of Caregiver or Study Partner With Responses to Home Administration Questionnaire (HAQ)

  Weeks 36, 52, 76, 104

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From day of first dose up to 16 weeks after the last dose (up to 120 weeks)

• Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)

  From day of first dose up to 16 weeks after the last dose (up to 120 weeks)

• Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)

  From day of first dose up to 16 weeks after the last dose (up to 120 weeks)

• Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)

  From day of first dose up to 16 weeks after the last dose (up to 120 weeks)

Study Arms (1)

Gantenerumab

EXPERIMENTAL

Participants will receive gantenerumab by subcutaneous (SC) injection at a dose of 120 mg every 4 weeks (Q4W) for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg every 2 weeks (Q2W) for another 12 weeks, followed by the target dose 255 mg once weekly (Q1W) for up to Week 103. Participants who complete Week 104 visit will be given an option to take part in 2-year extension of the study to receive gantenerumab 255 mg Q1W for up to Week 207.

Drug: Gantenerumab

Interventions

Gantenerumab DRUG

Gantenerumab will be administered by SC injection at a dose of 120 mg Q4W for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg Q2W for another 12 weeks, followed by the target dose 255 mg Q1W for up to Week 103 and an optional dose of 255 mg Q1W for up to Week 207.

Gantenerumab

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Probable Alzheimer's Disease (AD) dementia or prodromal AD.
• Availability of a reliable study partner (non-professional caregiver) who accepts to participate in study procedure throughout the study duration
• The participant should be capable of completing all aspects of study assessments including MRI, clinical genotyping, and PET imaging, either alone or with the help of the study partner (non-professional caregiver).
• Adequate visual and auditory acuitysufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted).
• Evidence of AD pathological process, as confirmed by amyloid PET scan by qualitative read by the core/central PET laboratory.
• Prodromal or mild symptomatology, as defined by a screening Mini-Mental State Examination (MMSE) score \>/=22 and Clinical Dementia Rating global score (CDR-GS) of 0.5 or 1.0, as well as a clinical dementia rating (CDR) memory domain score \>/=0.5.
• If the participant is receiving symptomatic AD medications, a stable dosing regimen for at least 3 months prior to screening and until start of study treatment.
• Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug.
• Agreement not to participate in other research studies for the duration of this trial, unless these are related Roche-sponsored non-interventional studies.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods hat result in a failure rate of \< 1% per year during the treatment period and for at least 16 weeks after the final dose of study drug.

You may not qualify if:

• Any evidence of a condition other than AD that may affect cognition.
• History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function.
• History or presence of clinically evident cerebrovascular disease.
• History or presence of posterior reversible encephalopathy syndrome.
• History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack.
• History of severe, clinically significant CNS trauma.
• History or presence of intracranial mass that could potentially impair cognition.
• Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae.
• History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits.
• History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder.
• At risk for suicide in the opinion of the investigator.
• Alcohol and/or substance abuse or dependants in past 2 years.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (34)

JEM Research LLC

Atlantis, Florida, 33462, United States

Location

ClinCloud, LLC

Maitland, Florida, 32751, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Alzheimer?s Research and Treatment Center

Wellington, Florida, 33414, United States

Location

Center for Advanced Research & Education

Gainesville, Georgia, 30501, United States

Location

Summit Research Network Inc.

Portland, Oregon, 97210, United States

Location

Abington Neurological Associates Willow Grove

Willow Grove, Pennsylvania, 19090, United States

Location

Jessa Zkh (Campus Virga Jesse)

Hasselt, 3500, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Groupement Hospitalier Est - Hôpital Neurologique; Neurologie A (U502)

Bron, 69677, France

Location

CH Pitie Salpetriere; IM2A

Paris, 75651, France

Location

Gerontopole; Centre de Recherche clinique

Toulouse, 31059, France

Location

Ambulates Gesundheitszentrum der Charité GmbH; MVZ Neurologie Campus Benjamin Franklin

Berlin, 12200, Germany

Location

ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic

Berlin, 13125, Germany

Location

Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie

München, 81675, Germany

Location

Ospedale Cardinale Panico; Dip.Ricerca Clinica in Neurologia ? UO Malattie Neurodegenerative

Tricase (LE), Apulia, 73039, Italy

Location

Ospedale San Giovanni Calibita Fatebenefratell;Neurologia

Rome, Lazio, 00186, Italy

Location

Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia

Milan, Lombardy, 20132, Italy

Location

NZOZ Vitamed

Bydgoszcz, 85-079, Poland

Location

Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.

Lublin, 20-410, Poland

Location

Senior Sp. Z O.O. Poradnia Psychogeriatryczna

Sopot, 81-855, Poland

Location

Centrum Medyczne Euromedis Sp. z o.o.

Szczecin, 70-111, Poland

Location

Centrum Medyczne NeuroProtect

Warsaw, 01-684, Poland

Location

NZOZ WCA

Wroc?aw, 53-659, Poland

Location

Policlínica Guipuzcoa; Servicio de Neurología

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital Quiron de Madrid; Servicio de Neurologia

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitario de la Princesa; Servicio de Neurologia

Madrid, 28006, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Neurologia

Madrid, 28041, Spain

Location

Hospital Universitari i Politecnic La Fe; Servicio de Neurología

Valencia, 46026, Spain

Location

Re-Cognition

Birmingham, B16 8QQ, United Kingdom

Location

Fritchie Centre

Cheltenham, GL53 9DZ, United Kingdom

Location

Ninewells Hospital

Dundee, DD12 9SY, United Kingdom

Location

Charing Cross Hospital; Imperial Memory Unit, Level 10 West

London, W6 8RF, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

gantenerumab

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 19, 2020
• Study Start: November 18, 2020
• Primary Completion: January 11, 2023
• Study Completion: March 15, 2023
• Last Updated: March 27, 2024
• Results First Posted: March 27, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

ES (5); PL (6); BE (3); IT (3); FR (3); US (7); DE (3); GB (4)